NCT03676322 - Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study of M5049 in Healthy Participants | Crick | Crick

Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study of M5049 in Healthy Participants

Phase 1CompletedNCT03676322

Merck KGaA, Darmstadt, Germany96 enrolled

Overview

The study will evaluate the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamics (PD), and explore the food effect of M5049 in healthy male and female participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

96

Conditions

Interventions

Participants will receive single ascending oral dose of M5049 in Part A. Participants will receive multiple ascending oral dose of M5049 once daily for 14 days or twice daily for 13 days followed by a single dose on Day 14 in the morning in Part B. Participants will receive a single oral dose of M5049 under fed conditions in Part C.

Participants will receive placebo matched to M5049.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Body weight between 50 to 100 kilogram (kg) * Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\^2) * Other protocol defined inclusion criteria could apply Exclusion Criteria: * History of clinically relevant disease of any organ system that may interfere with the objectives of the study or provide a risk to the health of the participant * History of splenectomy * History of epilepsy, other neurological disorders, or neuropsychiatric conditions * Other protocol defined exclusion criteria could apply

Locations (1)

Nuvisan GmbH

Neu-Ulm, Germany

Outcomes

Primary Outcomes

Part A: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

Time frame: Day 1 up to Day 21

Part A: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant changes will be reported.

Time frame: Day 1 up to Day 21

Part B: Occurrence and Severity of TEAEs and SAEs

Time frame: Day 1 up to Day 33

Part B: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant changes will be reported.

Time frame: Day 1 up to Day 33

Part C: Maximum Observed Plasma Concentration (Cmax) of M5049

Time frame: Pre-dose up to Day 6

Part C: Time to Reach Maximum Plasma Concentration (tmax) of M5049

Time frame: Pre-dose up to Day 6

Part C: Elimination Rate Constant (λz) of M5049

Time frame: Pre-dose up to Day 6

Part C: Apparent Terminal Half-life (t1/2) of M5049

Time frame: Pre-dose up to Day 6

Part C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049

Time frame: Pre-dose up to Day 6

Part C: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)

Data from ClinicalTrials.gov

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Secondary Outcomes

Part A: Maximum Observed Blood Concentration (Cmax) of M5049

Time frame: Pre-dose up to Day 6

Part A: Time to Reach Maximum Plasma Concentration (tmax) of M5049

Time frame: Pre-dose up to Day 6

Part A: Elimination Rate Constant (λz) of M5049

Time frame: Pre-dose up to Day 6

Part A: Apparent Terminal Half-life (t1/2) of M5049

Time frame: Pre-dose up to Day 6

Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049

Time frame: Pre-dose up to Day 6

Part A: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)

Time frame: Pre-dose up to Day 6

Part A: Total Body Clearance (CL/f) of M5049

Time frame: Pre-dose up to Day 6

Part A: Apparent Volume of Distribution (Vz/f) of M5049

Time frame: Pre-dose up to Day 6

Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/D) of M5049

Time frame: Pre-dose up to Day 6

Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/D) of M5049

Time frame: Pre-dose up to Day 6

Part A: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2

Time frame: Baseline, Day 2

Part A: Time Matched Plasma Concentration of M5049

Time frame: Pre-dose up to Day 6

Part B: Maximum Observed Blood Concentration (Cmax) of M5049

Time frame: Pre-dose up to Day 19

Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049

Time frame: Pre-dose up to Day 19

Part B: Elimination Rate Constant (λz) of M5049

Time frame: Pre-dose up to Day 19

Part B: Apparent Terminal Half-life (t1/2) of M5049

Time frame: Pre-dose up to Day 19

Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M5049

Time frame: Pre-dose up to Day 19

Part B: Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf)

Time frame: Pre-dose up to Day 19

Part B: Total Body Clearance (CL/f) of M5049

Time frame: Pre-dose up to Day 19

Part B: Apparent Volume of Distribution (Vz/f) of M5049

Time frame: Pre-dose up to Day 19

Part B: Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau)

Time frame: Pre-dose up to Day 19

Part B: Accumulation Ratio for Cmax (Racc Cmax) of M5049

Time frame: Pre-dose up to Day 19

Part B: Accumulation Ratio for AUCtau(Racc AUCtau) of M5049

Time frame: Pre-dose up to Day 19

Part B: Peak trough Ratio of M5049

Time frame: Pre-dose up to Day 19

Part B: Plasma Concentration Prior to the Next Dose (C trough) of M5049

Time frame: Pre-dose up to Day 19

Part B: Dose Normalized Maximum Observed Plasma Concentration at Steady State (Cmaxss/D) of M5049

Time frame: Pre-dose up to Day 19

Part B: Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/D) of M5049

Time frame: Pre-dose up to Day 19

Part B: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) on Digital Holter Electrocardiograms (ECG) at Day 2

Time frame: Baseline, Day 2

Part B: Time Matched Plasma Concentration of M5049

Time frame: Pre-dose up to Day 19

Part C: Occurrence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

Time frame: Day 1 up to Day 23

Part C: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant changes will be reported.

Time frame: Day 1 up to Day 23